The goal of this research is to elucidate fundamental principles governing the development of the visual system in primates including humans. Work on embryonic and fetal eye and visual brain centers directly in nonhuman primates is essential for the understanding of normal and pathological development of the visual system in man. The project consists of three integral parts conducted simultaneously: (1) normal prenatal development in rhesus monkey, (2) experimentally perturbed development in the monkey, and (3) correlation of development in monkey and human. In the first part, emphasis is on the mechanisms of neuronal genesis, migration, determination and differentiation including axonal growth and synaptogenesis in the retina, subcortical visual centers and visual cortex. In the second part, the consequences of selective destruction of visual centers and/or pathways sustained prenatally are evaluated in postnatal monkeys to determine the extent of neuronal plasticity and synaptic reorganization. Finally, in order to relate experimental data from nonhuman primates to man, we are performing correlative cytological analysis in both species using Golgi histochemistry and electron microscopy. The experimental analysis is conducted with a battery of modern neurological methods including 3H-thymidine autoradiography, Golgi impregnation, immunocytochemistry, electron microscopy, and retrograde, anterograde and transneuronal retrograde transport methods for tracing development of neuronal pathways. We have refined a prenatal neurosurgical procedure so that destruction and/or injection of radioactive tracers into selected brain regions during intrauterine life from the 50th day of pregnancy to birth is compatible with survival of fetus. Studies conducted this year include time of origin and cytology of interstitial neurons situated in the white matter subjacent to primary visual cortex, development of the superior colliculus, and genesis of afferent and efferent connections of the visual cortex in a series of fetal and postnatal monkeys.